[18F]FPRGD2 PET/CT imaging of integrin αvβ3 levels in patients with locally advanced rectal carcinoma

  • Nadia Withofs
  • Philippe Martinive
  • Jean Vanderick
  • Noëlla Bletard
  • Irène Scagnol
  • Frédéric Mievis
  • Fabrice Giacomelli
  • Philippe Coucke
  • Philippe Delvenne
  • Didier Cataldo
  • Sanjiv S. Gambhir
  • Roland Hustinx
Original Article

Abstract

Purpose

Our primary objective was to determine if [18F]FPRGD2 PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal cancer (LARC). Secondary objectives were to compare baseline [18F]FPRGD2 and [18F]FDG uptake, to evaluate the correlation between posttreatment [18F]FPRGD2 uptake and tumour microvessel density (MVD) and to determine if [18F]FPRGD2 and FDG PET/CT could predict disease-free survival.

Methods

Baseline [18F]FPRGD2 and FDG PET/CT were performed in 32 consecutive patients (23 men, 9 women; mean age 63 ± 8 years) with LARC before starting any therapy. A posttreatment [18F]FPRGD2 PET/CT scan was performed in 24 patients after the end of CRT (median interval 7 weeks, range 3 – 15 weeks) and before surgery (median interval 4 days, range 1 – 15 days).

Results

All LARC showed uptake of both [18F]FPRGD2 (SUVmax 5.4 ± 1.5, range 2.7 – 9) and FDG (SUVmax 16.5 ± 8, range 7.1 – 36.5). There was a moderate positive correlation between [18F]FPRGD2 and FDG SUVmax (Pearson’s r = 0.49, p = 0.0026). There was a moderate negative correlation between baseline [18F]FPRGD2 SUVmax and the TRG (Spearman’s r = −0.37, p = 0.037), and a [18F]FPRGD2 SUVmax of >5.6 identified all patients with a complete response (TRG 0; AUC 0.84, 95 % CI 0.68 - 1, p = 0.029). In the 24 patients who underwent a posttreatment [18F]FPRGD2 PET/CT scan the response index, calculated as [(SUVmax1 − SUVmax2)/SUVmax1] × 100 %, was not associated with TRG. Post-treatment [18F]FPRGD2 uptake was not correlated with tumour MVD. Neither [18F]FPRGD2 nor FDG uptake predicted disease-free survival.

Conclusion

Baseline [18F]FPRGD2 uptake was correlated with the pathological response in patients with LARC treated with CRT. However, the specificity was too low to consider its clinical routine use.

Keywords

RGD PET Rectal cancer Integrin Angiogenesis 

Notes

Acknowledgments

We thank the operators and Christine Mella (CYCLOTRON Research Centre), the technologists (Nuclear Medicine division), Isabelle Jupsin (Oncology Department), Kamilia Elkandoussi and Agnès Delga (Biobank, Pathology Department), Fabienne Perin (GIGA-Research, Laboratory of Tumour and Developmental Biology), Estelle Dortu and Chantal Humblet (GIGA-Research, Cytology and Histology Department), Laurence Seidel (Biostatistics Department) and Marcella Chavez (coordination of Translational Research in Oncology). Preliminary results were presented (as a poster) at the 2012 SNMMI Annual Meeting (Miami, Florida, US).

Compliance with ethical standards

Funding

The Belgian Fondation contre le Cancer and the federal Ministry of Health (Plan Cancer) supported the trial.

Conflicts of interest

None.

Ethical approval

The institutional Committee on Ethics approved the present prospective study protocol registered in the European Clinical Trials Database (EudraCT) under the reference number 2010-019219-39.

Informed consent

Every patient provided signed written informed consent.

Supplementary material

259_2015_3219_Fig5_ESM.jpg (8 kb)
Supplementary Fig. 1

Baseline [18F]FPRGD2 and FDG mean SUVmax in the primary rectal tumours in relation to TRG in the 32 included patients. The asterisk indicates a significant difference in the baseline SUVmax in comparison with TRG 0. The difference was significant with [18F]FPRGD2 SUVmax for TRG 1 (p = 0.0285), TRG 2 (p = 0.0150) and TRG 3 (p = 0.0420), while it was only significant with FDG for TRG 1 (p = 0.0104). (JPEG 8 kb)

259_2015_3219_MOESM1_ESM.tif (655 kb)
High resolution image (TIFF 655 kb)
259_2015_3219_Fig6_ESM.jpg (6 kb)
Supplementary Fig. 2

[18F]FPRGD2 mean response index (RI) in the primary rectal tumours in relation to TRG in the 24 patients in whom the posttreatment [18F]FPRGD2 PET/CT scan was available. (JPEG 6 kb)

259_2015_3219_MOESM2_ESM.tif (432 kb)
High resolution image (TIFF 432 kb)
259_2015_3219_Fig7_ESM.jpg (6 kb)
Supplementary Figure 3

Correlation between baseline and post-CRT [18F]FPRGD2 SUVmax in the primary LARC in the 24 patients in whom the posttreatment [18F]FPRGD2 PET/CT scan was available. (JPEG 5 kb)

259_2015_3219_MOESM3_ESM.tif (386 kb)
High resolution image (TIFF 385 kb)
259_2015_3219_Fig8_ESM.jpg (12 kb)
Supplementary Figure 4

Correlations between the baseline [18F]FPRGD2 and FDG PET/CT parameters related to tumour volume: a ITV70% and MTV40%, b TTI70% and TLG. (JPEG 12 kb)

259_2015_3219_MOESM4_ESM.tif (767 kb)
High resolution image (TIFF 767 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Nadia Withofs
    • 1
  • Philippe Martinive
    • 2
  • Jean Vanderick
    • 2
  • Noëlla Bletard
    • 3
  • Irène Scagnol
    • 3
  • Frédéric Mievis
    • 4
  • Fabrice Giacomelli
    • 4
  • Philippe Coucke
    • 2
  • Philippe Delvenne
    • 3
  • Didier Cataldo
    • 5
  • Sanjiv S. Gambhir
    • 6
  • Roland Hustinx
    • 1
  1. 1.Department of Medical PhysicsDivision of Nuclear Medicine and Oncological ImagingLiegeBelgium
  2. 2.Division of Radiation Oncology, Department of Medical PhysicsCHU LiègeLiègeBelgium
  3. 3.Department of PathologyCHU LiègeLiègeBelgium
  4. 4.CYCLOTRON Research CentreUniversity of LiègeLiègeBelgium
  5. 5.Laboratory of Tumour and Developmental Biology, GIGA-ResearchUniversity of LiègeLiègeBelgium
  6. 6.Molecular Imaging Program at Stanford (MIPS), Radiology DepartmentStanford UniversityStanfordUSA

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